Plasma protein N-glycan profiles are associated with calendar age, familial longevity and health

The development of medical interventions for the preservation of disease-free longevity would be facilitated by markers that predict healthy aging. Altered protein N-glycosylation patterns have been found with increasing age and several disease states. Here we investigate whether glycans derived from the total glycoprotein pool in plasma mark familial longevity and distinguish healthy from unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants in the Leiden Longevity Study (LLS) were obtained by glycan release, labeling and subsequent HPLC analysis with fluorescence detection. After normalization and batch correction, several regression strategies were applied to evaluate associations between glycan patterns, familial longevity and healthy aging. Two N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma of the offspring of long-lived individuals as compared to controls. These results were not confounded by the altered lipid status or glucose homeostasis of the offspring. Furthermore, a decrease in levels of LC-8 was associated with the occurrence of myocardial infarction (p = 0.049, coefficient = -0.065), indicating that plasma glycosylation patterns do not only mark familial longevity, but may also reflect healthy aging. In conclusion, we describe two glycan features, of which increased levels mark familial longevity while decreased levels of one of these features mark the presence of cardiovascular disease.Development and application of statistical models for medical scientific researc